The influence of in vivo and in vitro aging on the physicochemical properties of normal human erythrocytes will be studied in order to establish which physicochemical changes during the red cell aging process in vivo primarily control cell life span and senescent cell recognition by the reticuloendothelial system. The behavior of aged rhesus monkey red blood cells will be compared with that of human cells in order to develop a nonhuman primate model for in vivo studies of mechanisms of red cell aging. Affinity separation procedures such as two phase aqueous polymer partitioning will be developed for the fractionation of red cells according to age. The effectiveness of the fractionation procedures will be established by in vivo life span studies of radiolabelled fractionated red cells. Specific membrane modification techniques will be refined and employed to produce defined alterations in membrane properties which are indicated to be critical to the in vivo recognition and elimination of senescent red cells. In vitro tests including erythrophagocytosis will be refined for monitoring membrane alterations as reflected by variation in the biological behavior of the cells and for examining the probable roles of environmental conditions and humoral immunological factors in the red cell recognition and destruction process in vivo.